Transmission studies of potential human hepatitis agents were first reported in 1967 (Deinhardt 1967). Four tamarins inoculated with acute phase sera from a surgeon with acute hepatitis (patient GB) developed hepatitis, as did most tamarins inoculated in serial passage studies. Subsequent studies indicated that the etiological agent responsible for the development of hepatitis in these animals was not any of the known human hepatitis viruses (Purcell 1994). In 1995, two related RNA viruses named GB virus-B (GBV-B) and GB virus A (GBV-A) were identified in acute phase sera of a tamarin which developed hepatitis following inoculation with serum of the eleventh tamarin passage of the putative GB agent (Simons 1995a).
GBV-B infection of tamarins resulted in acute resolving hepatitis (Schlauder 1995, Buhk 1997). The natural host of GBV-B is still unknown as the virus has not been detected in uninoculated animals or in humans.
GBV-A, on the other hand, is an indigenous tamarin virus rather than a component of the original GB inoculum (Bukh 1997, Erker 1998). Experimental infection of tamarins with GBV-A did not produce hepatitis (Schlauder 1995). A human agent, GBV-C or hepatitis G virus, most closely related to GBV-A, was later identified (Simons 1995b, Linnen 1996). However, it is still not clear whether this virus actually causes hepatitis (Alter 1998, Bukh 1998a). Thus, of the known GB viruses, GBV-B may be the only true hepatitis virus.
Based on analysis of their genomic sequences, GBV-A, GBV-B and GBV-C were classified as members of the Flaviviridae family of viruses, and among the known viruses, GBV-B is the virus most closely related to hepatitis C virus (HCV) (Muerhoff 1995, Robertson 1998).
The GBV-B virus contains a positive-sense, single-stranded RNA genome of 9143 nucleotides (nts) (Simons 1995a, Muerhoff 1995). The viral genome of GBV-B consists of a 5′ untranslated region (UTR), a single long open reading frame (ORF) and a 3′ UTR. Based on known motifs, structural proteins were predicted to be encoded in the 5′ portion of the ORF and nonstructural (NS) proteins in the 3′ portion of the ORF (Muerhoff 1995). The hydropathy plots of the polyproteins of GBV-B and HCV are very similar even though the overall homology of the predicted polyproteins between GBV-B and HCV is only about 25–30% (Muerhoff 1995). The putative envelope proteins (E1 and E2) of GBV-B and HCV share common structural features, and significant homology was observed between the NS3 serine protease, the NS3 RNA helicase, and the NS5 RNA-dependent RNA polymerase regions of GBV-B and HCV (Muerhoff 1995). Furthermore, the function and substrate specificity of the GBV-B and HCV NS3 serine proteases are also similar (Scarselli 1997). The genomic structure and organization of GBV-B and HCV share additional features of interest. First, colinear regions with significant sequence homology were identified in the 5′ UTRs (Muerhoff 1995) and the predicted IRES structure of GBV-B is similar to that of HCV (Lemon 1997). Second, both viruses begin the 3′ UTR with a short sequence followed by a poly (U) stretch followed by additional nucleotides (50 nucleotides for GBV-B and 98 nucleotides for HCV). However, the 3′ terminal sequence of HCV forms a stable stem-loop structure (Kolykhalov 1996) whereas the published 3′ terminal sequence of GBV-B does not.
To date, molecular studies of HCV are severely limited by the lack of an efficient cell culture system for the virus and by expense and limited availability of chimpanzees, the sole animal model for HCV. Accordingly, a less expensive and more readily available animal than chimpanzees is necessary as an animal model for the study of HCV.